Design of experiment based validated stability indicating RP-HPLC method of temozolomide in bulk and pharmaceutical dosage forms
Author: Anam Khana, Syed Sarim Imamb, Mohd Aqila, Yasmin Sultanaa, Asgar Alia, Khalid Khanc
Abstract:
We have successfully developed and validated a precise and stability indicating RP-HPLC method for the determination of Temozolomide (TMZ) in both bulk samples and nanostructured lipid carriers. To optimize the chromatographic conditions, we employed a Box-Behnken statistical design with three factors and three levels. The separation was achieved using a solvent system combination of methanol:water (30:70) with acetic acid (0.25%).
The developed method underwent a comprehensive validation process in accordance with the ICH guidelines. It was evaluated for linearity, precision, accuracy, limit of detection, limit of quantitation, and robustness. The linearity of the method was established with a regression coefficient of 0.999 over a wide concentration range of 10-100 µg/mL. All validation parameters were found to be within the acceptable range.
Additionally, we conducted a degradation study of TMZ under different stress conditions. The results demonstrated the method's ability to accurately assess the amount of TMZ present even in the presence of potential degradants.
Overall, our developed RP-HPLC method provides a reliable and accurate means of quantifying TMZ in pharmaceutical formulations. Its stability indicating properties make it suitable for assessing the drug's stability and determining its concentration in various formulations.
Keywords
Statistical design; Optimization; Temozolomide; Validation; Stability
Citation: Anam Khana, Syed Sarim Imamb, Mohd Aqila, Yasmin Sultanaa, Asgar Alia, Khalid Khanc Design of experiment based validated stability indicating RP-HPLC method of temozolomide in bulk and pharmaceutical dosage forms doi:10.1016/j.bjbas.2015.11.011.
Received: 9 July 2015, Revised: 25 November 2015, Accepted: 28 November 2015, Available online: 8 April 2016
Copyright: © 2016 Beni-Suef University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Conclusions
Further, the method was optimized by design of experiment optimization technique using different variables. The measured signal was shown to be precise, accurate, and linear over the concentration range tested with a correlation coefficient better than 0.99. Moreover, the lower solvent consumption along with the short analytical run time of 3.8 min leads to a cost effective and environmentally friendly chromatographic procedure. The forced degradation studies showed well separation of parent peak from degradation metabolites. Thus, the above validated method is rapid, selective, specific, and accurate can be used for the separation of impurities and quantitative determination of TMZ in API and pharmaceutical formulations. The method demonstrated high degree of practical utility for estimation of TMZ in pharmaceutical dosage forms.
